The functional state of the LHRH and TRH neuronal terminals in the medial basal hypothalamus is determined predominantly by neural inputs from the anterior hypothalamic-preoptic region of the brain and by the neuroendocrine milieu. The goal for the research for the coming year is (1) to elucidate the mechanisms by which ovarian (estrogen, progesterone) and thyroid (thyroxine) hormones modulate the intracellular processing, storage, and relase of LHRH and TRH from hypothalamic neurons, and (2) to study the interrelationship between these processes as they occur in the anterior hypothalamic-preoptic and the medial basal hypothalamic regions, using synaptosomes and secretory granules as model systems. We propose to investigate the effects of these hormones on the sequestration of LHRH and TRH in secretory granules and synaptosomes in the anterior hypothalamic-preoptic and medial basal hypothalamic regions; the kinetics of the effects of the hormones will be determined. The role of the microtubule and neurofilament systems in the manifestations of these hormone actions will be evaluated. In addition, we will investigate the question of whether the hormone-induced modulation of the LHRH and TRH levels in the hypothalamic neurons is due to stimulation of the synthesis of these two peptides. Furthermore, we propose to investigate the possibility that after the in vivo initiation of hormonal action on the hypothalamic neurons, some of the intracellular processing of LHRH and TRH may proceed under in vitro conditions, thus, providing a system for the study of hormone action under defined and controlled conditions.